A Phase I/IIb extension study assessing the long-term safety and efficacy of an adeno-associated viral vector containing a codon-optimized human factor IX gene (AAV5-hFIX) previously administered to adult patients with severe or moderately severe haemophilia B during the CT-AMT-060-01 Phase I/II study.

Congenital haemophilia B is characterized by an increased bleeding tendency due
to either a partial or complete deficiency of the essential blood coagulation
Factor IX (FIX). Haemophilia B is an X-linked, recessive condition.
Approximately 1 in 25,000 live male newborns have haemophilia B. The number of
diagnosed haemophilia B patients globally is about 25,000. Individuals with
severe haemophilia B are usually diagnosed during the first year of life. The
severity of symptoms can vary, and the severe forms become apparent early in
life. Bleeding is the main symptom of the disease and usually increases when
the infant becomes mobile. Internal bleeding may occur anywhere and bleeding
into joints is common.
Haemophilia B is caused by a variety of genetic anomalies distributed
throughout the gene on the long arm of the X chromosome, with the most common
being single base-pair changes that result in missense, frame shift, or
nonsense mutations. With a deficiency or absence of FIX, activation of
coagulation factor X becomes severely impaired leading to delayed and
insufficient thrombin burst for normal haemostasis. The haemostatic plug formed
in these patients is fragile and easily dissolved by normal fibrinolytic
activity with impaired haemostasis, prolonged bleeding episodes and re-bleeding
as the consequences.
About 1/3 of individuals with haemophilia B have a severe disorder
characterized by functional FIX levels that are less than 1% of normal. Mild
and moderate haemophilia B are each observed in about 1/3 of patients.
Factor IX is synthesized as a single polypeptide chain that undergoes extensive
post-translational modifications. The liver is the primary site of FIX
synthesis and haepatocytes directly secrete FIX into the plasma.
Somatic gene therapy for haemophilia B offers the potential benefit for a shift
of the disease severity from severe to a moderate or mild haemophilia phenotype
through continuous endogenous production of FIX after a single administration
of vector. The identified risks are considered low and manageable and not
affecting the risk/benefit balance in an unfavorable way. CSL Behring*s
optimized AAV5 approach has the potential to further limit the risks currently
associated with AAV gene therapy approaches.
Interim results from the parent Phase I/II study (Study CT-AMT-060-01)
demonstrated that a single intravenous infusion of AMT-060, in patients with
moderately-severe to severe haemophilia B, was safe and well tolerated.
Patients demonstrated a modest increase in FIX activity, which was robust and
sustainable, resulting in a reduction/elimination in the use of FIX replacement
therapy and lowering the risk of spontaneous bleeding events over 4 years after
infusion. In addition, the level of FIX protein expression could be achieved
without inducing unacceptable alanine aminotransferase (ALT)/aspartate
aminotransferase (AST) elevations.
The purpose of this Phase I/IIb extension study is to assess the long-term
safety and efficacy of AMT-060 (6-10 years from the time of initial dosing),
and to further describe its safety profile and endogenous FIX activity.

This study has been transitioned to CTIS with ID 2024-512603-39-00 check the CTIS register for the current data.

Primary: To assess the long-term safety (6-10 years after dosing) of a systemic
administration of AAV5-hFIX, an AAV vector containing a codon-optimized human
coagulation hFIX gene, to adult subjects with severe or moderately severe
haemophilia B.
Secondary: To assess the long-term efficacy of a systemic administration of
AAV5-hFIX, an adeno-associated viral (AAV) vector containing a codon-optimized
human coagulation Factor IX (hFIX) gene, to adult subjects with severe or
moderately severe haemophilia B.

This is an open-label, extension study enrolling patients who have successfully
completed all assessments in Study CT-AMT-060-01 (Years 1-5). Patients will be
asked, during the final scheduled visit of the CT-AMT-060-01 study, to
participate in this study and give informed consent (within ± 2 weeks). There
will be no screening or baseline period. Patients will return to the same study
site every 6 months for safety and efficacy assessments. Patient-reported
outcome (PRO) assessments will be collected yearly at the study visit.
Assessment phase will begin at Visit 36 (the first clinical visit in this
extension study, approximately 5.5 years after the initial dosing visit Study
CT-AMT-060-01) and go to Visit 45 (10-years post-dosing in Study CT-AMT-060-01).
After giving consent, patients will enter the 5-year extension phase to
determine safety and efficacy of AMT-060. During this study, patients will
visit the same study site as in Study CT-AMT-060-01 every half year (6 months)
for evaluation of safety and efficacy parameters. Patients reported outcomes
will be completed yearly. Occurrence of adverse events (AEs) related to
previous AAV5-hFIX administration will be continuously monitored.

There will be a total of 10 scheduled study site visits. If the investigator
deems it necessary, there may be additional unscheduled visits. Procedures and
tests performed at the different visits include: Informed consent Procedure.
Review of concomitant treatment and adverse events. Physical examination. Blood
samples for variety of measurements. Abdominal ultrasound. Qol questionnaire
completion.

If this study shows positive results it could be the first step towards making
this product available to all patients with haemophilia B.However, there is no
guarantee that the subject will gain any benefit from this study.